Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells
Naringenin (NRG) was characterized for its ability to counteract mitochondrial dysfunction which is linked to cardiovascular diseases. The F1FO-ATPase can act as a molecular target of NRG. The interaction of NRG with this enzyme can avoid the energy transmission mechanism of ATP hydrolysis, especial...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933524000153 |
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| author | Salvatore Nesci Cristina Algieri Matteo Antonio Tallarida Rosita Stanzione Saverio Marchi Donatella Pietrangelo Fabiana Trombetti Luca D’Ambrosio Maurizio Forte Maria Cotugno Ilaria Nunzi Rachele Bigi Loredana Maiuolo Antonio De Nino Paolo Pinton Giovanni Romeo Speranza Rubattu |
| author_facet | Salvatore Nesci Cristina Algieri Matteo Antonio Tallarida Rosita Stanzione Saverio Marchi Donatella Pietrangelo Fabiana Trombetti Luca D’Ambrosio Maurizio Forte Maria Cotugno Ilaria Nunzi Rachele Bigi Loredana Maiuolo Antonio De Nino Paolo Pinton Giovanni Romeo Speranza Rubattu |
| author_sort | Salvatore Nesci |
| collection | DOAJ |
| description | Naringenin (NRG) was characterized for its ability to counteract mitochondrial dysfunction which is linked to cardiovascular diseases. The F1FO-ATPase can act as a molecular target of NRG. The interaction of NRG with this enzyme can avoid the energy transmission mechanism of ATP hydrolysis, especially in the presence of Ca2+ cation used as cofactor. Indeed, NRG was a selective inhibitor of the hydrophilic F1 domain displaying a binding site overlapped with quercetin in the inside surface of an annulus made by the three α and the three β subunits arranged alternatively in a hexamer. The kinetic constant of inhibition suggested that NRG preferred the enzyme activated by Ca2+ rather than the F1FO-ATPase activated by the natural cofactor Mg2+. From the inhibition type mechanism of NRG stemmed the possibility to speculate that NRG can prevent the activation of F1FO-ATPase by Ca2+. The event correlated to the protective role in the mitochondrial permeability transition pore opening by NRG as well as to the reduction of ROS production probably linked to the NRG chemical structure with antioxidant action. Moreover, in primary cerebral endothelial cells (ECs) obtained from stroke prone spontaneously hypertensive rats NRG had a protective effect on salt-induced injury by restoring cell viability and endothelial cell tube formation while also rescuing complex I activity. |
| first_indexed | 2024-03-08T00:01:19Z |
| format | Article |
| id | doaj.art-fa6f92a0d76e4bf882977013dbb4485a |
| institution | Directory Open Access Journal |
| issn | 0171-9335 |
| language | English |
| last_indexed | 2025-03-21T12:48:24Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj.art-fa6f92a0d76e4bf882977013dbb4485a2024-06-27T04:38:34ZengElsevierEuropean Journal of Cell Biology0171-93352024-06-011032151398Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cellsSalvatore Nesci0Cristina Algieri1Matteo Antonio Tallarida2Rosita Stanzione3Saverio Marchi4Donatella Pietrangelo5Fabiana Trombetti6Luca D’Ambrosio7Maurizio Forte8Maria Cotugno9Ilaria Nunzi10Rachele Bigi11Loredana Maiuolo12Antonio De Nino13Paolo Pinton14Giovanni Romeo15Speranza Rubattu16Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia 40064, Italy; Corresponding author.Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia 40064, ItalyRINA Consulting - Centro Sviluppo Materiali SpA, Via di Castel Romano 100, Rome, 00128, ItalyIRCCS Neuromed, Pozzilli 86077, ItalyDepartment of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona 60126, ItalyDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome 00189, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia 40064, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina 04100, ItalyIRCCS Neuromed, Pozzilli 86077, ItalyIRCCS Neuromed, Pozzilli 86077, ItalyDepartment of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona 60126, ItalyDepartment of Neuroscience, Mental Health, and Sensory Organs, Sapienza University, Rome 00189, ItalyDepartment of Chemistry and Chemical Technologies, University of Calabria, Cosenza 87036, ItalyDepartment of Chemistry and Chemical Technologies, University of Calabria, Cosenza 87036, ItalyTranslational Research Center, Maria Cecilia Hospital GVM Care & Research, Cotignola 48033, Italy; Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara 44121, ItalyMedical Genetics Unit, Sant’Orsola-Malpighi University Hospital, Bologna 40126, ItalyIRCCS Neuromed, Pozzilli 86077, Italy; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome 00189, ItalyNaringenin (NRG) was characterized for its ability to counteract mitochondrial dysfunction which is linked to cardiovascular diseases. The F1FO-ATPase can act as a molecular target of NRG. The interaction of NRG with this enzyme can avoid the energy transmission mechanism of ATP hydrolysis, especially in the presence of Ca2+ cation used as cofactor. Indeed, NRG was a selective inhibitor of the hydrophilic F1 domain displaying a binding site overlapped with quercetin in the inside surface of an annulus made by the three α and the three β subunits arranged alternatively in a hexamer. The kinetic constant of inhibition suggested that NRG preferred the enzyme activated by Ca2+ rather than the F1FO-ATPase activated by the natural cofactor Mg2+. From the inhibition type mechanism of NRG stemmed the possibility to speculate that NRG can prevent the activation of F1FO-ATPase by Ca2+. The event correlated to the protective role in the mitochondrial permeability transition pore opening by NRG as well as to the reduction of ROS production probably linked to the NRG chemical structure with antioxidant action. Moreover, in primary cerebral endothelial cells (ECs) obtained from stroke prone spontaneously hypertensive rats NRG had a protective effect on salt-induced injury by restoring cell viability and endothelial cell tube formation while also rescuing complex I activity.http://www.sciencedirect.com/science/article/pii/S0171933524000153mitochondriaF1FO-ATPasenaringeninpermeability transition poreROSSHRSP |
| spellingShingle | Salvatore Nesci Cristina Algieri Matteo Antonio Tallarida Rosita Stanzione Saverio Marchi Donatella Pietrangelo Fabiana Trombetti Luca D’Ambrosio Maurizio Forte Maria Cotugno Ilaria Nunzi Rachele Bigi Loredana Maiuolo Antonio De Nino Paolo Pinton Giovanni Romeo Speranza Rubattu Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells European Journal of Cell Biology mitochondria F1FO-ATPase naringenin permeability transition pore ROS SHRSP |
| title | Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells |
| title_full | Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells |
| title_fullStr | Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells |
| title_full_unstemmed | Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells |
| title_short | Molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on F1FO-ATPase and counteracting saline load-induced injury in SHRSP cerebral endothelial cells |
| title_sort | molecular mechanisms of naringenin modulation of mitochondrial permeability transition acting on f1fo atpase and counteracting saline load induced injury in shrsp cerebral endothelial cells |
| topic | mitochondria F1FO-ATPase naringenin permeability transition pore ROS SHRSP |
| url | http://www.sciencedirect.com/science/article/pii/S0171933524000153 |
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